Kidney transplant recipients are exposed to multiple factors that lead to osteoporosis after kidney transplantation. Recent short-term longitudinal studies revealed a strong decline of bone mineral density (BMD) within 1 year after transplantation. The long-term course of BMD after transplantation is still unknown. Therefore, we performed a cross-sectional study to determine BMD in 190 renal graft recipients (mean age 44 years, range 20-71 years) by dual-energy x-ray absorptiometry at various time intervals up to 20 years after transplantation (range 0-237 months). Mean BMD of graft recipients was lower than BMD values of an age- and sex-matched European reference collective at every time of measurement after renal transplantation (P < 0.01). Lowest mean BMD values were measured 12-24 months after transplantation. No loss of BMD occurred after the second posttransplant year beyond the normal age- and sex-dependent decline of BMD. Mean daily prednisone dosage was significantly higher within the first 2 posttransplant years compared with the later posttransplant period (13.1 +/- 6.2 vs. 6.7 +/- 3.4 mg/day). Other drugs or metabolic causes, including daily dosage of CsA, AZA, parathormone level, and graft function, did not show additional important differences before and after the second posttransplant year. Interpreting the results of a cross-sectional study in light of a time-dependent process, we suggest that the preexisting low BMD of kidney transplant recipients at the time of transplantation is further strongly reduced within the initial 2 posttransplant years, probably due mainly to the effect of prednisone therapy. After that time, when prednisone dosage is below a threshold of 7.5 mg/day, only a moderate, normal loss of BMD is apparent, even in patients up to 20 years after transplantation.